Abstract

Introduction: Due partly to their dissociative properties, ketamine and related new psychoactive substances (NPS) are widely used as recreational drugs. This has led to the discovery of a link between chronic use of ketamine and methoxetamine and the development of cystitis, characterized by chronic inflammation and urothelial ulceration. Recent findings indicate that ketamine has a direct toxic effect on human urothelial cells causing thinning of the urothelium within 3 days (1). We have developed a rat organ culture assay incubating ketamine or related NPS with rat bladder tissue, for up to 10 days, to establish whether NPS exhibit direct contact time effects. Methods: Rat bladder was dissected in half longitudinally and cultured at 37°C with 3mM ketamine or related NPS (methoxetamine, diphenidine, methoxphenidine) for 1, 3, 5 or 10 days. One half of each bladder was incubated with culture media (no drug) as time matched control. Bladders were then fixed in 10% formalin for 24 hours, dehydrated through graded alcohols and cleared with xylene, embedded in paraffin wax, sectioned at 5uM thickness and stained for visualisation of nuclei, cytoplasm, tight junctions and nitric oxide synthase. Results: Preliminary data indicates that after 3 days culture with ketamine there is thinning of rat bladder urothelium, loss of connective tissue and thickening of detrusor muscle. The effects of ketamine, methoxetamine, diphenidine and methoxphenidine on the integrity of urothelium cells, tight junctions and detrusor muscle will be presented.Conclusions: These results will provide insight into the long term effects of ketamine and NPS in the bladder, for which detailed information is lacking.(1) Baker et al., 2016 Ketamine-Induced Apoptosis in Normal Human Urothelial Cells Am J Pathology, 186 (5) 1268.